Selective Activation of Human Monocytes Exposed Ex Vivo to Different E-Cigarette Aerosols: Possible Role in Subclinical Inflammation

TL;DR

E-cigarette aerosols, especially certain flavors, can activate specific monocyte subsets, leading to inflammation and reduced immune function, which may pose long-term health risks.

Contribution

The study reveals that non-nicotine components in e-cigarette aerosols selectively activate monocytes, promoting pro-inflammatory and oxidative states.

Findings

E-cigarette aerosols increase adhesion markers, oxidative stress, and TNFα in small monocyte subsets.

Strawberry-flavored aerosols induce the strongest TNFα response in monocytes.

E-cigarette aerosols reduce phagocytic activity and drive monocytes toward macrophage-like, CD68-high states.

Abstract

What are the main findings?
Electronic cigarette aerosols, especially selected flavors, selectively activate small subsets of human monocytes, increasing adhesion markers, oxidative stress, TNFα, and CD68 expression while only modestly affecting whole-population cytotoxicity compared with cigarette smoke.These aerosols markedly reduce phagocytic activity and drive selected monocytes into highly oxidative/pro-inflammatory subsets that resemble macrophage-like, CD68-high cells, with effects largely attributable to non-nicotine aerosol constituents.

Electronic cigarette aerosols, especially selected flavors, selectively activate small subsets of human monocytes, increasing adhesion markers, oxidative stress, TNFα, and CD68 expression while only modestly affecting whole-population cytotoxicity compared with cigarette smoke.

These aerosols markedly reduce phagocytic activity and drive selected monocytes into highly oxidative/pro-inflammatory subsets that resemble macrophage-like, CD68-high cells, with effects largely attributable to non-nicotine aerosol constituents.

What are the implications of the main findings?
Vaping, though less globally toxic than cigarette smoke, can sustain subclinical inflammation by promoting adhesion-prone, pro-oxidative, TNFα-rich monocyte subsets that may preferentially accumulate at sites of vascular or tissue injury.Flavor-dependent monocyte activation suggests that certain e-cigarette products may carry underestimated long-term cardiopulmonary risk, particularly in chronic users, dual users, or individuals with pre-existing inflammatory or cardiovascular disease.

Vaping, though less globally toxic than cigarette smoke, can sustain subclinical inflammation by promoting adhesion-prone, pro-oxidative, TNFα-rich monocyte subsets that may preferentially accumulate at sites of vascular or tissue injury.

Flavor-dependent monocyte activation suggests that certain e-cigarette products may carry underestimated long-term cardiopulmonary risk, particularly in chronic users, dual users, or individuals with pre-existing inflammatory or cardiovascular disease.

Electronic cigarettes (ECs) are promoted as a safer alternative to traditional cigarettes, yet their impact on immune cells remains incompletely understood. This study investigates the activation of human primary adherent and non-adherent monocytes exposed ex vivo to aerosols from four flavored ECs (classic tobacco, menthol, watermelon, and strawberry) compared to cigarette smoke (CS) and nicotine alone. EC aerosols (ECEs) induced modest cytotoxicity, oxidative stress, and superoxide dismutase activity compared to CS, with high cell response heterogeneity indicating subpopulation-specific effects. Adherent monocytes showed elevated integrin expression (CD11a, CD11b), ICAM-1 (CD54), TNFα, and oxidative stress versus non-adherent cells, amplified by ECE. Dual fluorescence flow cytometry (green DCF for ROS and red for anti-TNFα Ab) revealed shifts toward pro-inflammatory/oxidative quadrants, particularly upper-right high-intensity relatively small subsets with macrophage M1-like CD68 expression in adherent cells. ECEs reduced phagocytosis in adherent monocytes, mimicking CS effects, probably driven by non-nicotine components. Strawberry flavor (ECE 4) elicited the strongest TNFα induction. These findings demonstrate EC-induced subclinical inflammation via selective monocyte activation, potentially contributing to chronic cardiopulmonary risks despite significantly lower overall toxicity than CS.

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